Using medical exome sequencing to identify the causes of neurodevelopmental disorders: Experience of 2 clinical units and 216 patients

被引：82

作者：

Cherot, E. ^{[1
,2
]}

Keren, B. ^{[3
,4
,5
]}

Dubourg, C. ^{[2
,6
]}

Carre, W. ^{[2
]}

Fradin, M. ^{[1
]}

Lavillaureix, A. ^{[3
]}

Afenjar, A. ^{[7
,8
,17
]}

Burglen, L. ^{[8
,17
]}

Whalen, S. ^{[8
,17
]}

Charles, P. ^{[3
,4
,7
]}

Marey, I. ^{[3
,4
,7
]}

Heide, S. ^{[3
,4
,7
]}

Jacquette, A. ^{[3
,4
,7
]}

Heron, D. ^{[3
,4
,7
]}

Doummar, D. ^{[5
,9
,10
]}

Rodriguez, D. ^{[5
,9
,10
]}

de Villemeur, T. Billette ^{[9
,11
]}

Moutard, M. -L. ^{[5
,9
]}

Guet, A. ^{[11
]}

Xavier, J. ^{[12
,13
,14
]}

Perisse, D. ^{[12
,13
]}

Cohen, D. ^{[12
,13
,14
]}

Demurger, F. ^{[1
]}

Quelin, C. ^{[1
]}

Depienne, C. ^{[3
,15
]}

Odent, S. ^{[1
,6
]}

Nava, C. ^{[3
,15
]}

David, V. ^{[2
,6
]}

Pasquier, L. ^{[1
,16
]}

Mignot, C. ^{[3
,4
,5
]}

机构：

[1] CLAD Ouest CHU Hop Sud, Serv Genet Med, Rennes, France

[2] CHU Pontchaillou, Lab Genet Mol & Genom, Rennes, France

[3] Hop La Pitie Salpetriere, AP HP, Dept Genet, Paris, France

[4] UPMC, Grp Rech Clin GRC Deficience Intellectuelle & Aut, Paris, France

[5] UPMC, Grp Rech Clin GRC ConCer LD, Paris, France

[6] Univ Rennes 1, CNRS UMR IGDR 6290, Rennes, France

[7] Hop La Pitie Salpetriere, Ctr Reference Deficiences Intellectuelles Causes, Paris, France

[8] Hop Armand Trousseau, AP HP, GHUEP, Ctr Reference Malformat & Malad Congenitales Cerv, Paris, France

[9] Hop Armand Trousseau, AP HP, Serv Neuropediat, Paris, France

[10] Hop Armand Trousseau, AP HP, Ctr Reference Neurogenet Enfant Adulte, Paris, France

[11] Hop Louis Mourier, AP HP, Serv Pediat, Colombes, France

[12] Grp Hosp Pitie Salpetriere, AP HP, Dept Child & Adolescent Psychiat, Paris, France

[13] Univ Paris 06, Paris, France

[14] UPMC, Sorbonne Univ, CNRS UMR 7222, Inst Syst Intelligents & Robot, Paris, France

[15] UPMC Univ Paris 06 UMR S 1127, Inst Cerveau & Moelle Epiniere, INSERM U1127, CNRS UMR 7225,Sorbonne Univ,ICM, Paris, France

[16] CHU Pontchaillou, INSERM CIC Pediat 1414, Rennes, France

[17] Hop Armand Trousseau, AP HP, Dept Genet, GHUEP, Paris, France

来源：

CLINICAL GENETICS | 2018年 / 93卷 / 03期

关键词：

autism; intellectual disability; medical exome; molecular strategy; INTELLECTUAL DISABILITY; MOLECULAR FINDINGS; ENCEPHALOPATHY; MUTATIONS; DIAGNOSIS; PHENOTYPE; STANDARDS; VARIANTS;

D O I：

10.1111/cge.13102

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Although whole-exome sequencing (WES) is the gold standard for the diagnosis of neurodevelopmental disorders (NDDs), it remains expensive for some genetic centers. Commercialized panels comprising all OMIM-referenced genes called medical exome (ME) constitute an alternative strategy to WES, but its efficiency is poorly known. In this study, we report the experience of 2 clinical genetic centers using ME for diagnosis of NDDs. We recruited 216 consecutive index patients with NDDs in 2 French genetic centers, corresponded to the daily practice of the units and included non-syndromic intellectual disability (NSID, n=33), syndromic ID (NSID=122), pediatric neurodegenerative disorders (n=7) and autism spectrum disorder (ASD, n=54). We sequenced samples from probands and their parents (when available) with the Illumina TruSight One sequencing kit. We found pathogenic or likely pathogenic variants in 56 index patients, for a global diagnostic yield of 25.9%. The diagnosis yield was higher in patients with ID as the main diagnosis (32%) than in patients with ASD (3.7%). Our results suggest that the use of ME is a valuable strategy for patients with ID when WES cannot be used as a routine diagnosis tool.

引用

页码：567 / 576

页数：10

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